Blood coagulation factor IX (F9) associated with hemostasis and coagulation is an essential blood coagulation factor that has been classically known, and it is well known as a causal protein of hemophilia. During the process of a blood coagulation reaction, F9 is cleaved at an intermediate portion (Activation peptide (F9-AP)) existing between the light chain and the heavy chain by blood coagulation factor XI (F11) and blood coagulation factor VII, and it then becomes activated. Even after the cleavage, the light chain is linked to the heavy chain via a disulfide bond, and F9 promotes blood coagulation as a single molecule (Non Patent Literature 1: Textbook of Medical Physiology, 10e. Arthur C. Guyton MD). However, there are almost no reports regarding the functions of F9-AP, which is an intermediate portion.
It should be noted that vascular endothelial cells, which constitute one type of epithelial cell, generally control platelet functions or the coagulation and fibrinolytic system, and act to prevent thrombus formation in the blood vessel. In addition, the inner surfaces of the blood vessels are coated with vascular endothelial cells, and this prevents the leakage of blood or the components thereof from the blood vessels. Various acute diseases result from damage to vascular endothelial cells (Non Patent Literature 2: Harrison's Principles of Internal Medicine, 18e. Dan Longo). Examples of the diseases resulting from damage to vascular endothelial cells include: acute coronary syndrome (ACS) such as myocardial infarction; disseminated intravascular coagulation syndrome (DIC), in which blood coagulation reactions that should occur only at bleeding sites randomly occur in the blood vessels throughout the whole body; septicemia, which is a systemic inflammatory response syndrome caused by bacteria; and anaphylaxis, which is an allergic disease exhibiting the most severe symptoms among allergic diseases. In these diseases, the extent of injury of endothelial cells is small. However, abnormal coagulation in blood vessels and the leakage of blood components from blood vessels occur. Since these symptoms are acute and severe, prompt and appropriate measures and administration of a therapeutic agent are required. In order to treat the acute stage of the aforementioned diseases, administration of an antihypertensive agent, anti-histamine, steroid, an anticoagulant drug, and other agents, as well as invasive treatments such as bypass surgery have been conventionally carried out. Although the above-mentioned diseases have each different causes, injury of vascular endothelial cells and the leakage of plasma components to stroma caused thereby are turning points for the determination of the prognosis of the diseases. Accordingly, it has been desired in clinical sites to develop a therapeutic agent capable of promptly repairing epithelial and endothelial injury and improving the functions thereof. However, none of the conventional therapeutic agents for epithelial and endothelial injury have provided prompt therapeutic effects.